Fragmented sleep is common in older humans; however, the severe sleep fragmentation of the Alzheimer patient is profoundly disruptive on a variety of levels. For caregivers, the patients' sleeping problems may present the most difficult behavioral characteristic of the disease. The fragmentation of sleep in the Alzheimer patient, characterized by frequent night time awakenings, may reflect disturbances of the circadian system. However, significant changes in slow wave sleep (SWS) and rapid eye movement (REM) sleep may also reveal additional molecular alterations, including cytokine dysregulation and cholinergic deficits. The proposed studies are aimed at understanding if changes in cytokine production play a role in changes in intrinsic sleep organization, including sleep fragmentation and changes in sleep architecture. The proposed studies will employ rats given amyloid B-protein to test the following hypotheses: l) Amyloid infusion into the lateral ventricle of the rat will disrupt sleep; 2) when administered into the lateral ventricle, sleep disruption will occur in the absence of an alteration in the circadian rhythms of the rat; 3) The amount of sleep disruption will be correlated with the histopathological demonstration of microglial activation and cytokine expression in periventricular areas. The Specific Aims of the proposal are, therefore, to: l) Document sleep disruption resulting from lateral ventricle ICV infusion of amyloid into the rat; 2) Determine whether this sleep disruption is accompanied by decreases in the amplitude of the circadian activity and body temperature rhythms; 3) Map microglial activation and cytokine expression in periventricular regions of the rat brain following ICV infusion of human amyloid beta-protein in the lateral-ventricle.